ABSTRACT - METHODOLOGY CORE Clinical research in total joint arthroplasty (TJA) demands the highest standards of study design while leveraging existing data sources and adopting standardized definitions and novel clinical research methodologies. TJA researchers need to be well-trained and supported if they are to respond effectively to current and emerging research gaps in TJA. The Mayo Core Center for Clinical Research in Total Joint Arthroplasty (CORE-TJA) Methodology Core will build upon Mayo?s existing methodology resources to advance the science of TJA clinical research at the national level by providing high-quality consulting, education and mentoring services, and state-of-the-art and novel methodology resources, facilitating optimal use of existing stand-alone or linked databases and clinical research networks, training of the next generation of TJA clinical investigators and building scientific collaborations. The Specific Aims of the CORE-TJA Methodology Core are: (1) To enhance TJA clinical research at the national level by providing consultation, education and mentoring services for TJA investigators, (2) To leverage existing databases and clinical research networks to identify the most informative study populations and study designs for TJA clinical research, and (3) To develop and disseminate novel methodologies applicable to observational and interventional study designs in TJA clinical research. Specifically, the Methodology Core will focus on 6 specific methodological areas in TJA research: methods to account for bias and confounding in TJA research, application of TJA-specific informatics tools for automated data extraction from the electronic health records, patient-reported outcomes research, clinical trials embedded in registries and/or healthcare systems, mixed- methods research and implementation research. The CORE-TJA Methodology Core will create a flexible, sustainable research infrastructure, trained workforce and synergistic collaborations at the national level.